C6—c10-dicarboxylic aciduria: investigations of a patient with riboflavin responsive multiple acyl-coa dehydrogenation defects

ABSTRACT Summary: The abnormal metabolites-adipic, suberic, and sebacic acids-were detected in large amounts in the urine of a boy during a Reye's syndrome-like crisis. Substantial

amounts of 5-OH-caproic acid, caproylglycine, glutaric acid, and 3-OH-butyric acid and moderately elevated amounts of ethylmalonic acid, methylsuccinic acid, 3-OH-isovaleric acid, and

isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack. 1-[14C]-Palmitic acid was

oxidized at a normal rate, whereas U-[14C]-Palmitic acid was oxidized at a reduced rate in cultured skin fibroblasts from the patient, thus indicating a defect at the level of medium- and/or

short-chain fatty acid oxidation. Riboflavin medication (100 mg three times a day) significantly reduced the excreted amounts of pathologic metabolites, suggesting a

flavineadeninedinucleotide-related acyl-CoA dehydrogenation defect as the cause of the disease. Carnitine in plasma was low in the patient (6 μmole/liter, controls 26–74 μmole/liter),

suggesting carnitine deficiency as a secondary effect of the acyl-CoA dehydrogenation deficiency. Speculation: The present patient, who presented with a Reye's syndrome-like attack,

suffers from impaired dehydrogenation of acyl-CoA resulting in accumulation of acyl-CoA in the cells. Attacks with similar symptoms are seen in other acyl-CoA dehydrogenation deficiencies,

such as glutaric aciduria types I and II, other types of C6—C10-dicarboxylic acidurias and isovaleric acidemia. Reduced flow through the acyl-CoA dehydrogenation steps may therefore be an

ethiologic factor in Reye's syndrome. Several of the accumulated acyl-CoA's are toxic and may be responsible for some of the symptoms. The low carnitine level in plasma and the

elevated esterified carnitine excretion in the present patient indicate that acyl-CoA accumulation may cause a functional carnitine deficiency by sequestration of carnitine as

acyl-carnitines. As the inborn defect, systemic carnitine deficiency may exhibit symptoms like those of Reye's syndrome, it may be speculated whether functional carnitine deficiency in

patients with accumulated acyl-CoA is another causal factor in the development of the symptoms during attacks. SIMILAR CONTENT BEING VIEWED BY OTHERS LABORATORY ANALYSIS OF ACYLCARNITINES,

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ARTICLE PDF AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Research Laboratory for Metabolic Disorders, University Department of Clinical Chemistry, Aarhus Kommunehospital, Aarhus N

Gregersen, H Wintzensen, S Kølvraa E. Christensen, M F Christensen, N J Brandt & K Rasmussen * Department of Pediatrics, Herning Hospital, Herning N Gregersen, H Wintzensen, S Kølvraa E.

Christensen, M F Christensen, N J Brandt & K Rasmussen * Institute of Human Genetics, University of Aarhus, Aarhus N Gregersen, N Gregersen, H Wintzensen, S Kølvraa E. Christensen, M F

Christensen, N J Brandt & K Rasmussen * Section of Clinical Genetics, University Department of Pediatrics and of Gynaecology and Obstetrics, Rigshospitalet, Copenhagen, Denmark N

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PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Gregersen, N., Wintzensen, H., E. Christensen, S. _et al._ C6—C10-Dicarboxylic Aciduria: Investigations of a Patient

with Riboflavin Responsive Multiple Acyl-CoA Dehydrogenation Defects. _Pediatr Res_ 16, 861–868 (1982). https://doi.org/10.1203/00006450-198210000-00012 Download citation * Issue Date: 01

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